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Biomedical subjects

R D Williams

Publications and source records attributed to R D Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

DNA ploidy and P-glycoprotein expression as predictive factors of response to neoadjuvant chemotherapy for invasive bladder cancer.

OBJECTIVE: To identify a factor or factors that could predict response of muscle invasive transitional cell carcinoma of the bladder to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy. METHODS: DNA ploidy analysis and immunohistochemical staining for p-glycoprotein (the product of the multidrug resistance gene, MDR-1) were performed on bladder biopsies obtained prior to chemotherapy. Radical cystectomy specimens were utilized for complete pathologic staging. RESULTS: Tissue was available for DNA ploidy analysis in 25 patients. Ten patients had complete responses to neoadjuvant chemotherapy and 15 patients did not respond. Nineteen patients had aneuploid tumors, of which 7 (37%) were complete responders. Six patients had diploid tumors, of which 3 (50%) were complete responders. This difference was not statistically significant. Tissue was available for immunostaining in 15 patients. Seven of 9 patients (78%) who did not respond to chemotherapy stained positively for p-glycoprotein, whereas 5 of 6 patients (83%) who had complete responses stained positively. This difference was not statistically significant. CONCLUSIONS: Neither DNA ploidy nor p-glycoprotein expression appears to predict successfully those patients likely to respond to neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy in the treatment of invasive bladder cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Absence of immunohistochemical metallothionein staining in bladder tumor specimens predicts response to neoadjuvant cisplatin, methotrexate and vinblastine chemotherapy.

Pre-chemotherapy bladder tumor tissue was retrospectively analyzed in 21 patients treated with neoadjuvant cisplatin, methrotrexate and vinblastine. Immunohistochemical staining for 2 proposed mediators of drug resistance, p-glycoprotein and metallothionein, was performed and compared to chemotherapeutic response and survival. There was no significant relationship between staining for p-glycoprotein and the response to chemotherapy or survival. Patients with no detectable staining for metallothionein were statistically more likely to sustain a complete pathological response (p = 0.029) after chemotherapy than those with any detectable staining. No relationship between metallothionein immunostaining and survival was apparent. This study offers further evidence linking metallothionein in tumor resistance to cisplatin containing chemotherapy regimens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Radioimmunoscintigraphy with 111indium labeled CYT-356 for the detection of occult prostate cancer recurrence.

We assessed the safety and ability of the 111indium labeled immunoconjugate 7E11-C5.3-glycyl-tyrosyl-(N,e-diethylenetriaminepentaacetic acid)-lysine (CYT-356) to detect sites of occult prostate cancer in 27 subjects who had undergone radical prostatectomy and whose only evidence of recurrent disease was an increasing (0.8 ng./ml. or greater) serum prostate specific antigen (PSA). All subjects underwent whole body scintigraphy between 2 and 4 days following the radiopharmaceutical injection. Routine blood work and human anti-mouse antibody titers were monitored. Scintigraphic findings were compared with clinical parameters, prostatic fossa biopsy results and conventional imaging techniques. Except for transient hypotension in 1 subject following the second infusion, no side effects or human anti-mouse antibody titers were detected. In 22 subjects 1 or more lesions were detected, of which 11 (50%) were confirmed by biopsy, computerized tomography or magnetic resonance imaging. Of 14 subjects with lesions in the prostatic fossa 13 had biopsies performed, 8 (62%) of which were positive. Magnetic resonance imaging confirmed tumor in the spine and chest computerized tomography findings were compatible with lesions seen in the mediastinum in 1 subject each. There was a statistically significant relationship between detecting a scan abnormality and the initial pathological stage of disease but not with the serum PSA. These data provide preliminary evidence that 111indium labeled CYT-356 can be safely administered and readministered, and it detects sites of occult prostate cancer recurrence in subjects whose PSA is increasing following radical prostatectomy.

Humans↗
PubMed1994

Phase II trial of 5-fluorouracil and alpha-2b interferon in patients with hormone-refractory metastatic prostate cancer.

OBJECTIVES: Metastatic prostate cancer remains a disease with no effective therapy. We treated 13 patients with hormone-refractory metastatic prostate cancer with 5-fluorouracil (5-FU) and alpha-2b interferon. Our objectives were to determine the response rate and toxicity of recombinant alpha interferon and 5-FU in patients with hormone-refractory metastatic prostate cancer. METHODS: Patients with progressive hormone-refractory metastatic prostate cancer with adequate hematologic and renal function underwent baseline bone scans, computed tomographic (CT) scans of abdomen and pelvis, and measurement of prostate-specific antigen (PSA). Therapy consisted of a 5-day loading course of 5-FU at 500 mg/m2 with alpha-2b interferon 9 million units subcutaneously 3 times weekly followed by weekly 5-FU and alpha interferon 3 times per week. RESULTS: When PSA was used as a response parameter with modified National Prostatic Cancer Project (NPCP) criteria, no objective responses were seen. Using NPCP criteria alone, 5 patients had stable disease. Post-therapy PSA values increased from baseline in 8 of 11 patients (2% to 72%) and declined in 3 patients (3% to 16%). Frequent dosage modifications were required with the dose intensity of 5-FU and alpha interferon of 57% and 58%, respectively. Toxicity was significant, with 31% of patients having grade 3 to 4 mucositis and 46% grade 3 to 4 fatique. CONCLUSIONS: 5-FU and alpha interferon, when administered at the dosage and schedule utilized in this study, have no clinically significant activity and are associated with unacceptable toxicity in patients with metastatic prostate cancer. The role of PSA as an indicator of response remains unclear.

Aged↗
PubMed1994

Culturally sensitive breast cancer screening programs for older black women.

Breast cancer is the leading cause of cancer mortality among black women. Elderly black women are particularly vulnerable and suffer the "double jeopardy" effect of older age and minority status. Older black women are not benefiting from the early detection provided through breast cancer screening. Factors that prevent this population from using breast cancer screening include cost, accessibility, availability, lack of knowledge, health care provider variables, and lack of community involvement. Breast cancer screening programs are needed that address cultural diversity to screen women who presently are not seen according to established guidelines. This article focuses on the need for primary care providers to offer culturally sensitive breast cancer screening programs designed for the older black woman. A model is presented based on Leininger's Culture Care Theory and the Health Belief Model. Specific strategies to increase the older black woman's participation in breast cancer screening practices are described.

Black or African American↗
PubMed1994

Teaching health promotion: motivating students through collaboration.

The collaborative model provided a number of benefits. Personalizing general health risks enabled the students to translate health promotion knowledge to individuals and groups in the community. The presence of the community health nurse permitted confidential dialogue with students regarding their personal appraisals. In the clinical setting the community health nurse served as a role model and demonstrated use of the tool among a variety of groups. Nurses are expected to identify populations at risk for various health problems and to promote healthful outcomes. This model was useful in assisting students to apply and synthesize health promotion concepts in an active and creative manner. Collaboration with an effective nurse role model was critical to the project.

Alabama↗
PubMed1994

The effect of benign breast biopsy on subsequent breast cancer detection practices.

PURPOSE/OBJECTIVES: To determine the effect of benign breast biopsy results on the frequency of subsequent breast self-examination (BSE), mammograms, and clinical examinations. DESIGN: Retrospective, descriptive design. SETTING: Two surgical oncology practices of an academic health science center in the southeastern United States and one surgical oncology practice and three family practices in another southern U.S. city. SAMPLE: A nonprobability sample consisting of 238 women with benign breast biopsies and a comparison group of 243 women with no histories of breast disease. METHODS: Questionnaires based on American Cancer Society (ACS) breast cancer detection guidelines were designed and mailed to all women who had benign breast biopsies within the past three years at the academic health science center. Similar questionnaires were mailed to women randomly selected from three family practices who had no histories of breast disease. Chi-square, Kruskal-Wallis one-way analysis of variance, and Wilcoxon matched pairs signed-ranks test were used in the data analysis. MAIN RESEARCH VARIABLES: Frequency of breast cancer detection practices including BSE, mammography, and clinical breast examinations. FINDINGS: In the group that had undergone biopsies, breast abnormalities were found by mammogram (38.8%), BSE (28.3%), clinical examination (16.9%), and accidental discovery (8.7%). The percentage of women performing monthly BSE increased from 47.4% to 67.3% postbiopsy (p < 0.0001). The frequency of mammography and clinical breast examinations also significantly increased postbiopsy (p < 0.0001). Similarly, the postbiopsy rate of BSE, mammography, and clinical breast examinations was higher than the rates for the control group. Women whose breast abnormalities were found by mammography became significantly more fearful of mammography (p < 0.05). CONCLUSIONS: Benign breast biopsies are associated with increased breast cancer detection practices. IMPLICATIONS FOR NURSING PRACTICE: All women need to follow ACS guidelines for breast cancer detection. Women who have undergone breast biopsy may be unduly afraid about the results of future detection practices and may need support and encouragement.

Adult↗
PubMed1994

Recombinant platelet factor 4 reversal of heparin in human cardiopulmonary bypass blood.

The ability of recombinant platelet factor 4, a protein of human origin with high heparin affinity, and the present clinical heparin reversal agent, protamine, to neutralize heparin in human whole blood was studied by means of three standard whole blood coagulation tests: whole blood clotting time, heparin assay, and activated clotting time. Ten subjects were chosen at random among patients undergoing cardiopulmonary bypass operations. Heparinized blood, free of protamine, was obtained from the bypass reservoir for testing. Whole blood aliquots, without reversal agents (controls) or with either protamine (10, 20, 30, or 40 micrograms/ml) or recombinant platelet factor 4 (10, 20, 40, or 80 micrograms/ml), were analyzed. The quantity of each agent required to reverse the ten samples, using 95% upper confidence bounds (t distribution) was determined for each method. Recombinant platelet factor 4 reversed heparin at 40 micrograms/ml and protamine at 20 micrograms/ml, suggesting a reversal ratio for recombinant platelet factor 4/protamine of 2:1 on a milligram basis. Further, currently available methods for testing coagulation should be reliable, without modification, to monitor the restoration of normal coagulation parameters with recombinant platelet factor 4 after cardiopulmonary bypass.

Blood Coagulation Tests↗
PubMed1993

Negative repeat transurethral resection of prostate fails to identify patients with stage A1 prostatic carcinoma at lower risk of progression: a long-term study.

Stage A1 (low-grade and low-volume) adenocarcinoma is associated with a low likelihood of progression. Repeat transurethral resection has been used to identify patients at increased risk (residual cancer noted) as well as those at low risk of progression (no residual cancer noted). We recently evaluated the ability of this technique to define a low-risk patient population. We reviewed the records of 24 patients who underwent repeat transurethral resection after they were identified as having Stage A1 prostatic cancer on initial resection (Gleason score < 5, tumor volume comprising < 5% of the resection specimen). Despite no evidence of residual carcinoma on repeat resection, 3 patients (13%) progressed at a mean follow-up of seven years (2 locally, 1 locally and distantly). We conclude that repeat resection does not effectively evaluate the risk of progression and that other techniques including transrectal ultrasonography and serial prostate-specific antigen measurements should be similarly evaluated.

Adenocarcinoma↗
PubMed1993

Neoadjuvant cisplatin, methotrexate and vinblastine for muscle-invasive bladder cancer: long-term followup.

A total of 26 patients with locally advanced bladder cancer received chemotherapy consisting of cisplatin, methotrexate and vinblastine. Radical cystectomy was performed in 24 of 26 patients (92%) receiving neoadjuvant therapy, with a pathological complete response in 6 (23%) and pathological partial response in 1 (4%) for an overall response rate of 35% (95% confidence limits 17 to 56%). The overall median survival time is currently undefined. Of the patients 15 (58%) are alive with a median followup of 48.6 months. Response rates from this neoadjuvant chemotherapy appear to be similar to those reported with methotrexate, vinblastine, doxorubicin and cisplatin, and may represent a therapeutically equivalent regimen but neither may be curative in the majority of the patients.

Adult↗
PubMed1993

Possible mechanism for seeding of tumor during radical prostatectomy.

Prostatic adenocarcinoma sometimes recurs locally in the operative bed after radical prostatectomy. Having observed local recurrence in several patients who had a small tumor confined to the prostate on whole mount serial sections, we postulated that some instances of local recurrence could arise from malignant cells shed in prostatic secretions expressed during surgery. To evaluate whether prostatic secretions contain malignant cells and to estimate the frequency of this phenomenon, we collected fresh prostatic secretions from radical prostatectomy specimens immediately after removal. The secretions were analyzed by cytology for the presence of malignant cells. Of 76 samples collected from consecutive patients with clinical stages T1 and T2 prostate cancer at 3 institutions 11 (14%) contained malignant cells. Positive cytology results were most frequent in patients with poorly differentiated tumors. Of 11 cancers with a Gleason sum of 8 to 10 in the prostatectomy specimen 6 (55%) had a positive cytology result. However, of 63 tumors with a Gleason sum of 5 to 7 only 4 (6%) were positive (p < 0.0001). There was no significant correlation with either clinical or pathological stage of the tumor in this small series. Our findings suggest that malignant cells shed during prostatectomy may seed the surgical bed and could be responsible for some instances of local tumor recurrence. The rate of positive cytology results in our study is similar to the local recurrence rates reported in the literature. Surgeons should make prudent attempts to avoid seeding from this source.

Adenocarcinoma↗
PubMed1993

Postoperative clostridium difficile gastroenteritis.

Clostridium difficile gastroenteritis can be the cause of an enigmatic postoperative syndrome of high temperature and marked leukocytosis, out of proportion to the initially mild constitutional symptoms. Patients may suffer delayed onset of diarrhea, which will test positive for the C. difficile enterotoxin by latex agglutination. We report 5 cases of C. difficile gastroenteritis that occurred within a 2-year period. We believe that the combination of preoperative bowel preparation, and intraoperative and postoperative systemic antibiotics is the primary operant factor. All patients responded rapidly when oral antibiotics specific for C. difficile were instituted. The sequelae of C. difficile colitis can include toxic megacolon with perforation and peritonitis, increasing the importance of early recognition and appropriate treatment.

Adult↗
PubMed1993

Magnetic resonance imaging for detection of prostate cancer metastatic to bone.

The diagnosis of prostate cancer metastatic to bone currently is made with plain x-rays, radionuclide bone scans, and acid and alkaline phosphatases. We used magnetic resonance imaging (MRI) in 18 patients with known prostate cancer to resolve conflicting evidence of metastases found on bone scans, plain films and serum enzyme determinations. Of 8 bone scans interpreted as positive MRI was read as negative for metastatic disease in 2. Of 5 negative bone scans 1 MRI study was interpreted as positive. All 5 equivocal bone scans demonstrated no osseous lesions on MRI. In addition, in 6 patients with evidence of bone metastases the serial MRI scans following hormonal therapy demonstrated radiographic and clinical improvement. We conclude that MRI is helpful in the diagnosis of metastatic prostate cancer when other radiographic examinations are enigmatic and that MRI can be used to determine the response to hormonal treatment.

Bone Neoplasms↗
PubMed1993

Localization of LAK cells and IL-2-stimulated regional lymph node lymphocytes by regional arterial infusion in renal tumor-bearing rats.

We describe the results of a traffic assay of the regional arterial administration of either lymphokine-activated killer cells or recombinant interleukin-2-activated regional lymph node lymphocytes in tumor-bearing rats in comparison with the results of systemic or intracardiac administration. The lymphocytes were labeled with 51Cr before infusion. The distribution and localization of these cells were serially evaluated by counting the radioactivity of the removed tissues. Concerning arterial administration, the labeled cells were directly infused into the abdominal aorta just proximal to the left renal artery. In the systemic or intracardiac route, the labeled cells preferentially localized to the lung, spleen and liver 2 h after injection. Radioactivity of the lung decreased thereafter and that of the spleen increased. In contrast, regional arterial administration yielded a remarkable accumulation of radioactivity in the left renal parenchyma 2 and 6 h after injection, similar to other distal organs tested. In the renal tumor model, the percentage radioactivity of the tumor tissue (% injectate recovered/g tissue) obtained at 6 h after injection in the arterial administration group ranged from 0.40 to 1.33, which was significantly higher (p < 0.05) than that in the systemic administration group. However, the radioactivity rapidly decreased from the tumor tissue 18 h after the injection. This study raises the essential issue on the mechanism of tumor destruction by lymphokine-activated killer lymphocytes in adoptive immunotherapy.

Animals↗
PubMed1992

When is intervention warranted?

A chemoprevention trial in prostate cancer would be a formidable but potentially rewarding study. The current status of knowledge of drug interactions with, biomarkers of, and even the natural history of prostate cancer is insufficient to study all levels of men at risk. Currently, the most promising group to study is group I--those men with a high probability of developing prostate cancer but who do not currently have evidence of the disease. This could be a placebo-controlled, prospective and randomized study with the endpoint being clinically-detected prostate cancer. In addition, much may be gained from short-term pilot studies of "chemo-active" agents on morphologic and other biomarkers of prostate cancer initiated immediately before surgical removal. It is hoped that such studies may provide rationale for future efforts directed at preventing progression of premalignant or early prostate cancer lesions.

Anticarcinogenic Agents↗
PubMed1992

Phase 1 trial of oral bropirimine in superficial bladder cancer.

A total of 34 patients with measurable superficial transitional cell cancer of the bladder entered into a phase 1, nonrandomized, noncomparative trial to assess the toxicity of the oral interferon inducer bropirimine. Of the patients 26 were also evaluable for response. The toxicity of bropirimine was minimal. At the 3-month evaluation 6 patients had experienced complete regression of tumor and had negative cytology studies, and 2 had partial responses. The majority of complete responses were in patients with carcinoma in situ only, with most responses seen at higher dose levels. One patient with papillary tumor and carcinoma in situ had a complete response. Some early responses appear to be durable. Most importantly, a high rate of complete response was noted at higher dose levels among patients who had failed prior therapy with bacillus Calmette-Guerin. Further clinical trials of bropirimine in bladder cancer appear warranted.

Administration, Oral↗